Photobiomodulation therapy modulates epigenetic events and NF-κB expression in oral epithelial wound healing
The aim of this study was to evaluate the effect of photobiomodulation therapy (PBMT) on histone 3 acetylation (acH3) and NF-κB expression during oral ulcer healing. A total of 48 male Wistar rats were divided into control group (CG) and PBMT group (n = 24 each). Traumatic ulcers were created in the dorsum of the rats’ tongue with a punch tool. Irradiation with InGaAlP laser, 660 nm, 40 mW, 0.04 cm2 spot size, 4 J/cm2, 4 s, and 0.16 J per spot was performed once a day in close contact for 10 consecutive days. CG received only daily handling. Rats were euthanized on days 3, 5, and 10 (n = 8) and were monitored daily to assess wound status. Immunohistochemical analysis for acH3 and NF-κB detection was performed. One thousand epithelial cells were counted, and mean acH3- and NF-κB-positive cells were calculated and compared between the groups. PBMT accelerated the repair of oral ulcers. On day 3, PBMT showed significantly higher means for acH3- and NF-κB-positive cells than CG. On day 5, no difference was observed between the groups concerning both markers. On day 10, PBMT presented lower acH3 and NF-κB means than the control group. We concluded that PBMT stimulates keratinocyte migration in the early stage of oral wound healing and keratinocyte differentiation at the final stage by modulating histone acetylation and NF-κB expression.
KeywordsLow-level laser therapy Diode laser Repair Histone acetylase enzyme Histones deacetylase enzyme
The authors are grateful to Marta Justina Giotti Cioato and Flavia Rejane Giusti for technical support.
This study was funded by the Postgraduate Research Group of Porto Alegre Clinics Hospital (GPPG/FIPE: 2014-0534), Brazilian National Council for Scientific and Technological Development (CNPq student scholarship), Children’s Cancer Institute (student scholarship), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-finance code 001. Manoela Domingues Martins is a research fellow funded by the Brazilian National Council for Scientific and Technological Development (CNPq).
Compliance with ethical standards
The study was approved by the ethics committee of Porto Alegre Clinics Hospital (Brazil) under process number 14-0534. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed involving animals were in accordance with the ethical standards of the institution, which the study was conducted.
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.Dongong TI, Meirong LU, Xiaobing FU, Weindon H (2014) Causes and consequences of epigenetic regulation in wound healing. Wound Rep Reg 22(3):305–312Google Scholar
- 7.Spallota F, Cencioni C, Straino S, Sbardella G, Castellano S, Capogrossi MC, Martelli F, Gaetano C (2013) Enhancement of lysine acetylation accelerates wound repair. Communicative & Integrative Biology 6(5):e25466Google Scholar
- 11.Lawrence T (2009) The nuclear factor NFk-B pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):1–10Google Scholar
- 15.Martins MD, Fernandes KPS, Pavesi VC, França MC, Mesquita-Ferrari RA, Bussadori SK (2011) Healing properties of papain-based gel on oral ulcers. Braz J Oral Sci 10(1):120–123Google Scholar
- 16.Bourguignon-filho AM Feitosa ACR, Beltrão GC, Pagnoncelli RM (2005) Utilização do laser de baixa intensidade no processo de cicatrização tecidual. Revisão de literatura. Revista Portuguesa de Estomatologia, Medicina Dentária e Cirurgia Maxilofacial 46(1): 37-43Google Scholar
- 24.Sperandio FF, Simões A, Corrêa L, Aranha AC, Giudice FS, Hamblin MR, Sousa SC (2015) Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair. J Biophotonics 8(10):795–803Google Scholar
- 25.Antunes HS, Wajnberg G, Pinho MB, Jorge NAN, de Moraes JLM, Stefanoff CG, Herchenhorn D, Araújo CMM, Viégas CMP, Rampini MP, Dias FL, de Araujo-Souza PS, Passetti F, Ferreira CG (2018) cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study. Lasers Med Sci 33(1):11–18PubMedGoogle Scholar
- 26.Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, Serrera-Figallo MA, Gutiérrez-Pérez JL, Torres-Lagares D (2018) Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized controlled trial. Int J Oral Maxillofac Surg S0901-5027(18):30475–30472Google Scholar
- 28.Huynha NC-N, Evertsb V, Ampornaramveth RS (2017) Histone deacetylases and their roles in mineralized tissue regeneration. Bone Rep 16(7):33–40Google Scholar
- 31.Lewis CJ, Mardaryev AN, Sharov AA, Fessing MY, Botchkarev VA (2014) The epigenetic regulation of wound healing. Adv Wound Care 3(7):468–474Google Scholar
- 38.Rahmana I, Marwickb J, Kirkhamc P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kB and pro-inflammatory gene expression. Biochem Pharmacol 68(6):1255–1267Google Scholar
- 40.Na J, Shin JY, Jeong H, Lee JY, Kim BJ, Kim WS, Yune TY, Ju B-G (2017) JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing. Sci Rep N7(1):6494Google Scholar
- 41.Curra M, Pellicioli ACA, Kretzmann Filho NA, Ochs G, Matte U, Sant’Ana Filho M, Martins MAT, Martins MD (2015) Photobiomodulation reduces oral mucositis by modulating NF-kB. J Biomed Opt 20(12):125008Google Scholar